A Novel Anti-PD-L1 Vaccine for Cancer Immunotherapy and Immunoprevention
by
Jie Chen 1,†, Hui Liu 2,†, Tiffany Jehng 2, Yanqing Li 1, Zhoushi Chen 1
, Kuan-Der Lee 3, Hsieh-Tsung Shen 3,4, Lindsey Jones 2, Xue F. Huang 1,* and Si-Yi Chen 2,*
Jie Chen 1,†, Hui Liu 2,†, Tiffany Jehng 2, Yanqing Li 1, Zhoushi Chen 1, Kuan-Der Lee 3, Hsieh-Tsung Shen 3,4, Lindsey Jones 2, Xue F. Huang 1,* and Si-Yi Chen 2,*
1
Pomona Biotechnology Corp., 605 E Huntington Drive, Monrovia, CA 91016, USA
2
Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, 1450 Biggy St, Los Angeles, CA 90033, USA
3
Department of Hematology and Oncology, Taipei Medical University Hospital and Department of Medicine, Taipei Medical University, Taipei 110, Taiwan
4
Jiyan Biomedical Corp., Taipei 110, Taiwan
*
Authors to whom correspondence should be addressed.
†
These two authors contributed equally to this work.
Cancers 2019, 11(12), 1909; https://doi.org/10.3390/cancers11121909
Received: 20 September 2019 / Accepted: 22 November 2019 / Published: 1 December 2019
Dendritic cells (DCs) are potent antigen-presenting cells that play a critical role in activating cellular and humoral immune responses. DC-based tumor vaccines targeting tumor-associated antigens (TAAs) have been extensively tested and demonstrated to be safe and potent in inducing anti-TAA immune responses in cancer patients. Sipuleucel-T (Provenge), a cancer vaccine of autologous DCs loaded with TAA, was approved by the United States Food and Drug Administration (FDA) for the treatment of castration-resistant prostate cancer. Sipuleucel-T prolongs patient survival, but has little or no effect on clinical disease progression or biomarker kinetics. Due to the overall limited clinical efficacy of tumor vaccines, there is a need to enhance their potency. PD-L1 is a key immune checkpoint molecule and is frequently overexpressed on tumor cells to evade antitumor immune destruction. Repeated administrations of PD-L1 or PD-1 antibodies have induced sustained tumor regression in a fraction of cancer patients. In this study, we tested whether vaccinations with DCs, loaded with a PD-L1 immunogen (PDL1-Vax), are able to induce anti-PD-L1 immune responses. We found that DCs loaded with PDL1-Vax induced anti-PD-L1 antibody and T cell responses in immunized mice and that PD-L1-specific CTLs had cytolytic activities against PD-L1+ tumor cells. We demonstrated that vaccination with PDL1-Vax DCs potently inhibited the growth of PD-L1+ tumor cells. In summary, this study demonstrates for the first time the principle and feasibility of DC vaccination (PDL1-Vax) to actively induce anti-PD-L1 antibody and T cell responses capable of inhibiting PD-L1+ tumor growth. This novel anti-PD-L1 vaccination strategy could be used for cancer treatment and prevention.
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Keywords:
PD-L1; dendritic cells; tumor vaccine; immune checkpoint; immunotherapy
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MDPI and ACS Style
Chen, J.; Liu, H.; Jehng, T.; Li, Y.; Chen, Z.; Lee, K.-D.; Shen, H.-T.; Jones, L.; Huang, X.F.; Chen, S.-Y. A Novel Anti-PD-L1 Vaccine for Cancer Immunotherapy and Immunoprevention. Cancers 2019, 11, 1909.
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